The inhibin protein family includes dimeric glycoproteins produced by the gonads which act in an endocrine fashion to suppress secretion of follicle stimulating hormone (FSH) from the pituitary gland. Since FSH is the major hormone involved in stimulation of ovulation and sperm production, inhibin-induced suppression of FSH diminishes the rates of ovulation and sperm production. Inhibins are therefore natural suppressers of the reproductive process.
Active immunization of farm animals against inhibin increases the rates of ovulation and sperm production, demonstrating that inhibin-based immunogens are important agents to enhance fertility in farm animals, including swine, bovine, ovine, and equine animals. See, for example: Brown, et al., J.Reprod.Fertility 90:199-205, 1990; King, et al., J.Animal Science 71:975-982, 1993; Morris, et al., J.Reprod.Fertility 97:255-261, 1993; McCue, et al., Theriogenology 38:823-831, 1992; Voglmayer, et al., Biol.Reprod. 42:81-86, 1990; Martin, et al., Biol.Reprod. 45:73-77, 1991.
The immunization of gilts with a small peptide fragment of the bovine inhibin .alpha..sub.c.sup.1-26 subunit chemically conjugated to human alpha globulin (HAG) and mixed with Freund's adjuvant resulted in a minor increase in FSH during the follicular phase and a decrease in FSH during the luteal phase, without effect on serum concentrations of estradiol, progesterone, or luteinizing hormone (King, et al., J. Animal Science 71:975-982, 1993). Despite the relatively minor increase in FSH during the follicular phase and decrease during the early luteal phase, immunized gilts had a 39% greater ovulation rate as compared with controls. In addition, lifetime proliferacy of the immunized gilts was enhanced.
While the above described merits of using the antigenic inhibin peptide to neutralize inhibins and enhance fertility are known, a commercially useful vaccine is not available.
The development of vaccines based on small antigenic epitopes is hampered by the inability of the small antigen to elicit a good immune response in a host animal. The use of carrier immunogens provides some assistance in the immune response, but often decreases the specific activity and yield of the response against the desired antigen. Methods for conjugation of antigens to carrier agents are costly, and generally utilize hazardous chemicals. Covalent coupling of antigen to a carrier protein is inherently variable, resulting in an antigen with an imprecise structure, compromising vaccine potency. The use of adjuvants also tends to decrease the yield of specific antibodies and can be harmful to the animal host, causing abscesses, skin lesions, and hypersensitivity. These factors are unacceptable for the production of a commercially useful vaccine.
These disadvantages are overcome in the present invention by using recombinantly produced fusion proteins as immunogens, whose structure is well defined. Synthesis of the inventive immunogens does not require hazardous chemical treatments, and the molecules are herein demonstrated to induce a desired anti-inhibin immune response, even in the absence of additional adjuvants.